Statin Dose Research Articles

Addition of Bempedoic Acid to Statin-Ezetimibe versus Statin Titration in Patients with High Cardiovascular Risk: A Single-Centre Prospective Study.

Reducing levels of low-density lipoprotein cholesterol (LDL-C) below recommended thresholds is a core component of cardiovascular prevention strategies. We hypothesized that the addition of bempedoic acid to patients already on statin-ezetimibe therapy was more effective than titrating the statin dose in reducing LDL-C. The study enrolled 120 patients at high cardiovascular risk and with LDL-C above 70 mg/dL. They were randomly divided into two groups: the bempedoic acid (BA) group, taking bempedoic acid in addition to statin plus ezitimibe, and the statin titration (ST) group, including patients who doubled the dose of statin. At 12 weeks, the BA group presented a more significant decrease in LDL-C compared to the ST group (-22.9% vs. 7.5% p 0.002). The total cholesterol decreased significantly in the BA group compared to ST (-14.8% vs.-4.7%; p 0.013) No significant between-group changes in HDL and triglycerides occurred. At 12 weeks, the number of patients who reached LDL-C lower than 70 mg/dL was 38 (63%) in the BA group versus 22 (37%) in the ST group (between groups, p 0.034). In the BA group, the LDL-lowering effect of bempedoic acid was similar between patients taking atorvastatin and rosuvastatin. No side effects occurred during the follow up period. In conclusion, the addition of bempedoic acid to statin-ezetimibe combined treatment was more effective than doubling the dose of statin in reducing LDL-C levels and increased the number of patients reaching the LDL-C goal.

Early statin use is associated with improved survival and cardiovascular outcomes in patients with atrial fibrillation and recent ischaemic stroke: A propensity-matched analysis of a global federated health database.

Statins reduce recurrent stroke and cardiovascular events in patients with non-cardioembolic stroke. The benefits of statins in patients with AF and recent IS remain unclear. We aimed to investigate the benefits of statins in patients with AF and recent IS. This retrospective, cohort study was conducted using deidentified electronic medical records within TriNetX platform. Patients with AF and recent IS, who received statins within 28 days of their index stroke were propensity score-matched with those who did not. Patients were followed up for up to 2 years. Primary outcomes were the 2-year risk of recurrent IS, all-cause mortality and the composite outcome of all-cause mortality, recurrent IS, transient ischaemic attack (TIA), and acute myocardial infarction (MI). Secondary outcomes were the 2-year risk of TIA, intracranial haemorrhage (ICH), acute MI, and hospital readmission. Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (95%CI). Of 20,902 patients with AF and recent IS, 7500 (35.9%) received statins within 28 days of their stroke and 13,402 (64.1%) did not. 11,182 patients (mean age 73.7 ± 11.5; 5277 (47.2%) female) remained after propensity score matching. Patients who received early statins had significantly lower risk of recurrent IS (HR: 0.45, 95%CI: 0.41-0.48, p < 0.001), mortality (HR: 0.75, 95%CI: 0.66-0.84, p < 0.001), the composite outcome (HR: 0.48, 95%CI: 0.45-0.52, p < 0.001), TIA (HR: 0.37, 95%CI: 0.30-0.44, p < 0.001), ICH (HR: 0.59, 95%CI: 0.47-0.72, p < 0.001 ), acute MI (HR: 0.35, 95%CI: 0.30-0.42, p < 0.001) and hospital readmission (HR: 0.46, 95%CI: 0.42-0.50, <0.001). Beneficial effects of early statins were evident in the elderly, different ethnic groups, statin dose intensity, and AF subtypes, large vessel occlusion and embolic strokes and within the context of statin lipophilicity, optimal LDL-cholesterol levels, various cardiovascular comorbidities, treatment with intravenous thrombolysis or endovascular thrombectomy, and NIHSS 0-5 and NIHSS > 5 subgroups. Patients with AF and recent IS, who received early statins, had a lower risk of recurrent stroke, death, and other cardiovascular outcomes including ICH, compared to those who did not.

The Effect of Statins on Carotid Intima-Media Thickness and C-Reactive Protein in Type 2 Diabetes Mellitus: A Meta-Analysis.

The effect of statins on CIMT progression and C-reactive protein (CRP) in T2DM patients is widely reported. However, some studies demonstrated no effect of statins on CIMT and CRP in T2DM patients, while others reported otherwise. Thus, the current study comprehensively and quantitatively analyzes data from previous studies to evaluate the overall effect of statins on CIMT and CRP in T2DM to rule out any inconsistencies observed in previous clinical evidence. Therefore, the aim of this meta-oanalysis was to evaluate the effect of statins on CIMT progression and CRP in T2DM. A comprehensive search for studies was performed using PubMed, Scopus, Web of Sciences, and the Cochrane Library, for publications from their inception to 16 July 2024. The meta-analysis was conducted using Jamovi (version 4.2.8) and Review Manager (version 5.4), with the overall effect sizes reported as standardized mean differences (SMD) and 95% confidence intervals (CI). Evidence from eleven studies (fifteen statin dosages) that met the inclusion criteria with a sample size of 983 T2DM patients on statin treatment was analyzed. The overall effect size from the random effect model meta-analysis showed a reduction in the CIMT status amongst T2DM patients post-statin treatment compared to at baseline [SMD = -0.47, 95%CI (-0.76, -0.18), p = 0.001]. Furthermore, there was a reduction in the level of CRP in T2DM patients post-treatment [SMD = -1.80, 95% CI (-2.76, -0.84), p < 0.001]. Evidence gathered in this study suggests that statin therapy effectively reduces CIMT and CRP levels among patients living with T2DM. Interestingly, this evidence suggests that 20 mg of atorvastatin is more effective in reducing CIMT and CRP. Therefore, we recommend conducting further trials with larger sample sizes and proper methodology for T2DM.

LIpid Response to Statins ± Ezetimibe In Mumbai (LIRIM): A Cross-sectional Observational Study.

India has the highest burden of cardiovascular disease (CVD) among developing nations. Data from international studies show significant underimplementation of recommended aggressive lipid-lowering strategies for achieving low-density lipoprotein cholesterol (LDL-C) goals, especially after percutaneous coronary intervention (PCI), a pattern also observed in India. Moreover, ethnic variation in response to statin therapy has prompted clinicians to adopt lower doses of statin therapy in Asians to achieve comparable LDL-C lowering. To document the dose of statin ± ezetimibe required to achieve the European Society of Cardiology (ESC) goals of LDL-C <55 mg/dL in Indian patients with established atherosclerotic cardiovascular disease (ASCVD). This retrospective single-center, cross-sectional, observational, all-comers study in Mumbai evaluated the dose of atorvastatin (A)/rosuvastatin (R) ± ezetimibe (E) treatment at which patients with established ASCVD (n = 542), irrespective of their baseline level, achieved LDL-C goals (<55 mg/dL). Those with LDL-C levels >55 mg/dL on current therapy were switched to R 40 mg ± E 10 mg daily. The final data set (n = 340) included those who achieved LDL-C goals at the initial visit and those at follow-up. The primary and secondary outcomes assessed the impact of R 40 mg ± E 10 mg (R40 ± E10) on LDL-C (<55 mg/dL) and non-high-density lipoprotein cholesterol [non-HDL-C (<85 mg/dL)] goal achievement, respectively. At the end of follow-up, LDL-C <55 mg/dL was observed in 42.16% of patients (n = 113) with R40 and in another 43.28% (n = 116) with R40 + E10. A few patients (n = 39; 14.6%) achieved this goal with other dosages. Similarly, non-HDL-C <85 mg/dL was observed in 39.3% of patients (n = 107) with R40 and in another 47.4% of patients (n = 129) with R40 + E10. Overall, around 20% of patients were unable to achieve their LDL-C and non-HDL-C goals despite being on high-intensity statin ± E therapy. In the first report of its kind in India, this study showed that suboptimal LDL-C goal achievement occurred in around 20% of high-risk ASCVD patients on dual therapy. This indicates that clinicians should consider the addition of other therapies [e.g., bempedoic acid, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and inclisiran] to mitigate the residual risk. Several more trials are needed to determine the most suitable treatment regimen for this population.

A hospital lipid-lowering protocol improves 2-year clinical outcomes in patients with acute coronary syndrome.

Although mortality after acute coronary syndrome (ACS) has improved in the acute phase, cardiovascular events occur at a certain frequency in the chronic phase. A hospital lipid-lowering protocol (HLP) could be effective in providing optimal lipid-lowering therapy to improve long-term clinical outcomes after ACS. This study investigated the impact of HLP on clinical outcomes in patients with ACS. We retrospectively analysed 1,114 ACS patients who had undergone successful percutaneous coronary intervention between November 2011 and June 2021. In December 2018, we introduced a HLP that included the prescription of the maximum tolerated dose of statin, ezetimibe, and eicosapentaenoic acid after ACS treatment. We compared 2-year clinical outcomes before (control group: 791 patients) and after the HLP's introduction (HLP group: 323 patients). The primary outcome was the non-target vessel revascularisation (non-TVR) rate. A multivariate Cox proportional hazard model and inverse probability weighting (IPW) based on the propensity score were used to evaluate the effect of HLP on the outcomes. The cumulative 2-year non-TVR incidence was significantly lower in the HLP group than in the control group (8.5% vs 13.8%; p=0.019). Multivariable analysis revealed non-TVR risk was significantly lower in the HLP group than in the control group (adjusted hazard ratio [aHR]: 0.637 [95% confidence interval [CI]: 0.416-0.975]; p=0.038). The IPW analysis confirmed a significant association between the HLP and a lower non-TVR risk (aHR: 0.544 [95% CI: 0.350-0.847]; p=0.007). Implementing HLP for ACS patients improved the 2-year clinical outcome.

Rationale for Increasing Doses of Statins in Everyday Clinical Practice

HMG-CoA reductase inhibitors (statins) were discovered in the early 1970s in Japan and were originally used to treat patients with hereditary hyperlipidemia. In the late 1990s and early 2000s, clinical trials using statins for primary and secondary prevention showed the possibility of reducing cardiovascular (CV) and, in some cases, all-cause mortality. Intensive statin therapy (atorvastatin 80 mg/day and rosuvastatin 40 mg/day) compared to initial doses provides an additional 16% reduction in CV complications. Regression studies with the original rosuvastatin using intracoronary ultrasound and other modern methods have shown the possibility of stabilization and regression of atherosclerosis in the carotid and coronary arteries. High-dose statin therapy is generally well tolerated; the incidence of clinically significant adverse liver reactions does not exceed 2-3 per 100,000 people, and the incidence of myopathies with increased creatine kinase over 10 upper limits of normal is not higher than 1 per 10,000 people per year. Long-term statin treatment does not increase the risk of dementia and, in some studies, reduced the risk of Alzheimer's disease. Achieving target levels of low-density lipoprotein cholesterol (LDL-C) in routine practice does not exceed 5-11%; one of the main reasons for that is the rare (2-3%) prescription of high doses of statins. Increasing statin doses in routine clinical practice will optimize the treatment of patients with high CV risk and will contribute to further reduction of mortality in our country.

EXPRESS: Short-term Efficacy of Moderate Intensity Rosuvastatin in COVID-19 Patients: A Randomized Clinical Trial.

As the COVID-19 pandemic persists, the exploration of adjunct therapies to mitigate disease severity remains a priority. Statins, known for their pleiotropic effects, have been under investigation for their potential role in managing COVID-19 complications. The study was conducted in a single referral hospital and adhered to Consolidated Standards of Reporting Trials (CONSORT) guidelines. Eligible participants were randomized in a 1:1 ratio into either the rosuvastatin group or the control group. Outcome measures included vital signs, laboratory data, clinical outcomes, and patient symptoms. Statistical analysis was performed using SPSS software. A total of 100 patients were enrolled. No significant differences were observed between the rosuvastatin and control groups in terms of baseline characteristics and laboratory parameters, except for the fact that rosuvastatin-treated patients showed lower levels of C-reactive protein (CRP) in comparison with the controls on both the first and fifth days (38.1 ± 16.3 vs. 50.5 ± 25.3) compared to the control group. Clinical outcomes, including hospital length of stay, Intensive Care Unit (ICU) admission, need for intubation, and 1-month mortality, did not differ significantly between the two groups. Symptom scales, as assessed by the Borg Rating of Perceived Exertion (Borg RPE) and Leicester Cough Questionnaire (LCQ), showed significant improvement in the rosuvastatin group compared to controls. Our study provides insights into the short-term efficacy of moderate-intensity rosuvastatin in COVID-19 patients. Further research is warranted to elucidate the long-term effects and optimal dosing of statins in COVID-19 management.

Evolocumab (Repatha)

It is recommended that Repatha be reimbursed by public drug plans for the reduction of elevated low-density lipoprotein cholesterol (LDL-C) in adult patients with primary hyperlipidemia (atherosclerotic cardiovascular disease [ASCVD]) if certain conditions are met. Repatha should only be covered to treat patients with a recent acute coronary syndrome (ACS) event, defined as those who have been hospitalized for a heart attack or unstable angina in the past 52 weeks. Additionally, these are patients with an LDL-C level between 1.8 mmol/L and 2.2 mmol/L (inclusive) or a non–high-density lipoprotein cholesterol (non–HDL-C) level between 2.6 mmol/L and 2.9 mmol/L (inclusive) or an apolipoprotein B (ApoB) level between 0.7 g/L and 0.8 g/L (inclusive), despite receiving the highest dose of statin that can be tolerated and ezetimibe. Alternatively, these are patients with an LDL-C level greater than 2.2 mmol/L, a non–HDL-C greater than 2.9 mmol/L, or an ApoB greater than 0.8 g/L, despite receiving the highest dose of statin that can be tolerated, with or without ezetimibe. Repatha should only be reimbursed if prescribed by a cardiologist or internal medicine specialist with expertise in the post-ACS setting and if the cost of Repatha is reduced. Repatha should not be reimbursed for use in combination with other PCSK9 inhibitors.

Machine learning to optimise statin therapy using real-world primary care outcomes: can statin doses be reduced in some patients?

Machine learning to optimise statin therapy using real-world primary care outcomes: can statin doses be reduced in some patients?

Effects of combining ezetimibe with high dose statin on endothelial function in patients underwent percutaneous coronary intervention

Effects of combining ezetimibe with high dose statin on endothelial function in patients underwent percutaneous coronary intervention

A Rapid and Scalable Multiplex PCR-Based Next-Generation Amplicon Sequencing Method for Familial Hypercholesterolemia Genetic Screening.

Familial hypercholesterolemia (FH) is a frequently underdiagnosed genetic disorder characterized by elevated low-density lipoprotein (LDL) levels. Genetic testing of LDLR, APOB, and PCSK9 genes can identify variants in up to 80% of clinically diagnosed patients. However, limitations in time, scalability, and cost have hindered effective next-generation sequencing of these genes. Additionally, pharmacogenomic variants are associated with statin-induced adverse effects in FH patients. To address these challenges, we developed a multiplex primer-based amplicon sequencing approach for FH genetic testing. Multiplex primers were designed for the exons of the LDLR, APOB, and PCSK9 genes, as well as for pharmacogenomic variants rs4149056 (SLCO1B1:c.521T > A), rs2306283 (SLCO1B1:c.388A > G), and rs2231142 (ABCG2:c.421C > A). Analytical validation using samples with known pathogenic variants and clinical validation with 12 FH-suspected probands were conducted. Library preparation was based on a bead-based tagmentation method, and sequencing was conducted on the NovaSeq 6000 platform. Our approach ensured no amplicon dropouts, with over 100× coverage on each amplicon. Known variants in 2 samples were successfully detected. Further, we identified one heterozygous LDLR (p.Glu228Ter) variant and 2 homozygous cases of LDLR (p.Lys294Ter) and LDLR (p.Ser177Leu) variants in patients. Pharmacogenomic analysis revealed that overall 3 patients may require reduced statin doses. Our approach offered reduced library preparation time (approximately 3 h), greater scalability, and lower costs (under $50) for FH genetic testing. Our method effectively sequences LDLR, APOB, and PCSK9 genes including pharmacogenomic variants that will guide appropriate screening and statin dosing, thus increasing both efficiency and affordability.

Gender disparities in utilization of statins for low density lipoprotein management across the spectrum of atherosclerotic cardiovascular disease: Insights from the houston methodist cardiovascular disease learning health system registry

IntroductionLower statin utilization is reported among women compared to men, however large-scale studies evaluating gender disparities in LDL-C management in individuals with ASCVD and its subtypes remain limited, particularly across age and racial/ethnic subgroups. In this study, we address this knowledge gap using data from a large US healthcare system. MethodsAll adult patients with established ASCVD in the Houston Methodist Learning Health System Registry during 2016–2022 were included. Statin use and dose were extracted from the database. The association between gender and statin utilization was evaluated using multivariate logistic regression analyses in patients with ASCVD overall, across ASCVD subtypes, and by age, racial/ethnic subgroups, and socioeconomic risk factors. ResultsA total of 97,819 patients with prevalent ASCVD were included. Women with ASCVD had lower utilization of any statin (64.3% vs 72.6 %; p < 0.001) and high-intensity statin (29.8% vs 42.5 % p < 0.001) compared with men. In fully adjusted models, women had 40 % lower odds of any (adjusted odds ratio [aOR]:0.58, 95 % CI 0.57–0.60) and high-intensity statin use (aOR:0.59, 0.57–0.61) relative to men. Women were also less likely to have guideline-recommended LDL-C < 70 mg/dL (30.2% vs 42.7 %; p < 0.01). These differences persisted across age, racial/ethnic and socioeconomic subgroups. ConclusionSignificant gender disparities exist in contemporary lipid management among patients with ASCVD, with women being less likely to receive any and high-intensity statin and achieving guideline defined LDL-C goal compared with men across age and racial/ethnic subgroups. These disparities underscore the need to further understand potential socioeconomic drivers of the observed lower statin uptake in women.

Association of Statin Use with Dementia Risk Among Older Adults in Japan: A Nested Case-Control Study Using the LIFE Study.

Previous studies have shown a possible association between statin use and a decreased risk of dementia, but the association has not been sufficiently established, especially in the super-aging society of Japan. This study aimed to determine the association between statin use and the risk of dementia among Japanese participants aged> =65 years old. Data from the Longevity Improvement and Fair Evidence (LIFE) Study were utilized, including medical and long-term care (LTC) claim data from 17 municipalities between April 2014 and December 2020. A nested case-control study was conducted with one case matched to five controls based on age, sex, municipality, and year of cohort entry. We used a conditional logistic regression model to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs). This study included 57,302 cases and 283,525 controls, with 59.7% of the participants being woman. After adjusting for potential confounders, statin use was associated with a lower risk of dementia (OR, 0.70; 95% CI: 0.68-0.73) and Alzheimer's disease (OR: 0.66; 95% CI: 0.63-0.69). Compared with non-users, the ORs of dementia were as follows: 1.42 (1.34-1.50) for 1-30 total standardized daily dose (TSDD), 0.91 (0.85-0.98) for 31-90 TSDD, 0.63 (0.58-0.69) for 91-180 TSDD, and 0.33 (0.31-0.36) for >180 TSDD in dose-analysis. Statin use is associated with a reduced risk of dementia and Alzheimer's disease among older Japanese adults. A low cumulative statin dose is associated with an increased risk of dementia, whereas a high cumulative statin dose is a protective factor against dementia.

Therapeutic Monoclonal Antibodies for Metabolic Disorders: Major Advancements and Future Perspectives.

Globally, the prevalence of metabolic disorders is rising. Elevated low-density lipoprotein (LDL) cholesterol is a hallmark of familial hypercholesterolemia, one of the most prevalent hereditary metabolic disorders and another one is Diabetes mellitus (DM) that is more common globally, characterised by hyperglycemia with low insulin-directed glucose by target cells. It is still known that low-density lipoprotein cholesterol (LDL-C) increases the risk of cardiovascular disease (CVD). LDL-C levels are thought to be the main therapeutic objectives. The primary therapy for individuals with elevated cholesterol levels is the use of statins and other lipid lowering drugs like ezetimibe for hypercholesterolemia. Even after taking statin medication to the maximum extent possible, some individuals still have a sizable residual cardiovascular risk. To overcome this proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors-monoclonal antibodies (mAbs) are a novel class of systemic macromolecules that have enhanced LDL-C-lowering efficacy. Along with this other inhibitor are used like Angiopoeitin like 3 inhibitors. Research on both humans and animals has shown that anti-CD3 antibodies can correct autoimmune disorders likediabetes mellitus. Individuals diagnosed with familial hypercholesterolemia (FH) may need additional treatment options beyond statins, especially when facing challenges such as statin tolerance or the inability of even the highest statin doses to reach the desired target cholesterol level. Here is the summary of PCSK9, ANGPTL-3 and CD3 inhibitors and their detailed information. In this review we discuss the details of PCSK9, ANGPTL-3 and CD3 inhibitors and the current therapeutic interventions of using the monoclonal antibodies in case of the metabolic disorder. We further present the present studies and the future prospective of the same.

Efficacy of Alirocumab, Evolocumab, and Inclisiran in Patients with Hypercholesterolemia at Increased Cardiovascular Risk.

Background and Objectives: Lowering low-density lipoprotein (LDL-C) levels is critical for preventing atherosclerotic cardiovascular disease, yet some patients fail to reach the LDL-C targets despite available intensive lipid-lowering therapies. This study assessed the effectiveness and safety profile of alirocumab, evolocumab, and inclisiran in lipid reduction. Materials and Methods: A cohort of 51 patients (median (Q1-Q3) age: 49.0 (39.5-57.5) years) was analyzed. Eligibility included an LDL-C level > 2.5 mmol/L while on the maximum tolerated dose of statin and ezetimibe, a diagnosis of familial hypercholesterolemia, or a very high risk of cardiovascular diseases following myocardial infarction within 12 months prior to the study. Follow-ups and lab assessments were conducted at baseline (51 patients), 3 months (51 patients), and 15 months (26 patients) after the treatment initiation. Results: Median initial LDL-C levels 4.1 (2.9-5.0) mmol/L, decreasing significantly to 1.1 (0.9-1.6) mmol/L at 3 months and 1.0 (0.7-1.8) mmol/L at 15 months (p < 0.001). Total cholesterol also reduced significantly compared to baseline at both intervals (p < 0.001). No substantial differences in LDL-C or total cholesterol levels were observed between 3- and 15-month observations (p > 0.05). No statistically significant differences were noted in cholesterol reduction among the alirocumab, evolocumab, and inclisiran groups at 3 months. The safety profile was favorable, with no reported adverse cardiovascular events or significant changes in alanine transaminase, creatinine, or creatine kinase levels. Conclusions: Alirocumab, evolocumab, and inclisiran notably decreased LDL-C and total cholesterol levels without significant adverse effects, underscoring their potential as effective treatments in patients who do not achieve lipid targets with conventional therapies.

A systematic review of the drug-drug interaction between Statins and Quinolones

BackgroundStatins are widely used in cardiovascular disease (CVD) as a common lipid-lowering drug, while quinolones are widely used for the treatment of infectious diseases. It is common to see CVD in combination with infectious diseases, therefore it is often the case that statins and quinolones are used in combination. Data suggest combinations of statin and quinolone may be associated with potentially life-threatening myopathy, rhabdomyolysis and acute hepatitis. This systematic review aims to characterize data regarding patients affected by the statin-quinolone interaction.MethodsThe purpose of this systematic review was to collect and evaluate the evidence surrounding statin-quinolone drug interactions and to discuss related risk mitigation strategies. The following databases were searched: PubMed (Medline), Embase, Scopus, and Cochrane Library. The systematic electronic literature search was conducted with the following search terms. In this study, three types of search terms were used: statins-related terms, quinolones-related terms, and drug interactions-related terms.ResultsThere were 16 case reports that met the criteria for qualitative analysis. Patients were involved in the following adverse reactions: rhabdomyolysis (n = 12), acute hepatitis (n = 1), muscle weakness (n = 1), hip tendinopathy (n = 1), or myopathy (n = 1). In the included literature, patients vary in the dose and type of statins they take, including simvastatin (n = 10) at a dose range of 20–80 mg/d and atorvastatin (n = 4) at a dose of 80 mg/d. There were 2 patients with unspecified statin doses, separately using simvastatin and atorvastatin. The quinolones in combination were ciprofloxacin (n = 9) at a dose range of 800–1500 mg/d, levofloxacin (n = 6) at a dose range of 250–1000 mg/d, and norfloxacin (n = 1) in an unspecified dose range. 81% of the case patients were over 60 years of age, and about 1/3 had kidney-related diseases such as diabetic nephropathy, post-transplantation, and severe glomerulonephritis. Nearly two-third of the patients were on concomitant cytochrome P450 3A4 (CYP3A4) inhibitors, P-glycoprotein (P-gp) inhibitors, or organic anion transporting polypeptide 1B1 (OATP1B1) inhibitors.ConclusionPatients treated with statin-quinolone combination should be monitored more closely for changes in aspartate aminotransferase or creatine kinase (CK) levels, and muscle symptoms, especially in patients with ciprofloxacin or levofloxacin, with simvastatin and high-dose atorvastatin, over 60 years of age, with kidney-related diseases, and on concomitant CYP3A4 inhibitors.

The Effect of Atorvastatin Intensity, Obesity, Gender, and Age upon New-onset Type 2 Diabetes Incidence among Libyan Coronary Heart Disease Patients

Background: Atorvastatin is one of the statins family of lipid-lowering drugs. Statin has been linked to protective actions against cardiovascular disease; however, the use of statin has been linked to an increased risk of diabetes. Aim of the study: To assess the prevalence of diabetes following the use of Atorvastatin and also to evaluate the effect of the statin intensity, BMI, age, and gender upon the glycemic control and incidence of diabetes. Material and methods: 200 CHD patients divided into 2 groups. The atorvastatin group (using Atorvastatin (40 or 80 mg/day) for&lt;2 months and the control group (non-atorvastatin users). FBG, HbA1c, total cholesterol, triglyceride, ALT, and AST were investigated, and BMI was calculated for all participants. Results: Generally, the NOD incidence was 17% (17 patients had NOD out of 100 Atorvastatin-consuming patients), whereas, there were no NOD cases in the non-Atorvastatin group (100 cases). The oldest age ( ≥ 70 years) Atorvastatin-using patients showed the highest incidence of NOD (43.8%). The NOD incidence was higher in the male group with 22 NOD cases (27.5%) than that of the female group which showed 3 NOD cases (15%). Regarding the effect of BMI, the obese group (BMI ≥ 30) showed a higher incidence of NOD (23 cases, 45.1%) than the non-obese group (BMI&lt;30) which showed 13 NOD cases (26.5%) of the atorvastatin using patients. In regards to statin intensity, the 80 mg/day-Atorvastatin subgroup showed 7 NOD cases (30%) which was higher than the 40 mg/ day-Atorvastatin subgroup which showed 18 NOD cases (23%) of the atorvastatin using patients. Conclusion: Atorvastatin treatment was significantly implicated in the development of NOD. NOD incidence increases with higher doses of statin. The risk of NOD was also affected by other factors including; obesity, gender, and old age.

The early after discharge cardiac CT for low-risk chest pain study: the ED-CT study.

An accelerated diagnostic pathway is created to aid the management of low-risk patients presenting to the emergency room with chest pain. Records are taken of patient outcomes and factors influencing physician decision-making between inpatient invasive angiography versus early outpatient cardiac CT angiography. A cohort study at 30 days post discharge is undertaken over 1 year. Differences are observed between a population of patients who underwent early outpatient CT and a population of ambulatory haemodynamically stable patients who underwent inpatient fluoroscopic angiography. Totally, 369 patients underwent CT (F = 46%) and 37 underwent angiography (F = 30%). Median outpatient CT was at 14 days. At 30 days, 0 patients suffered mortality or myocardial infarction. Eleven percent were recommended for invasive angiography. Two percent of CT patients underwent coronary revascularization. Median calcium score was 0. Twenty percent of the CT population were commenced on high-potency statin or had their pre-existing statin dose intensified. Calcium score affected a composition of statin commencement, angiography, and revascularization (OR 59, P < .001). Age, troponin, vascular disease, and previous coronary revascularization appeared to influence choice between coronary computed tomography angiography (CCTA) and invasive angiography. An accelerated diagnostic pathway for outpatient cardiac CT for chest pain resulted in no mortality or myocardial infarction, with a low level of downstream testing and coronary revascularization. At a median time to CCTA of 14 days post discharge from the emergency department, there is no effect on patient major adverse cardiac events.

Rare Clinically Significant Idiosyncratic Drug Induced Liver Injury Caused by Low Dose Atorvastatin: Time for a New Approach to Surveillance and Risk Identification

Background: Atorvastatin is a member of the class of cholesterol lowering drugs called statins, which works by inhibiting HMG-CoA reductase, an enzyme involved in cholesterol synthesis in the liver. Statins are used to reduce the risk of cardiovascular events in individuals who have risk factors or a history of cardiovascular disease. While atorvastatin is generally well-tolerated, like all statins, it can have some adverse effects, including Drug induced liver injury (DILI) which is rare and often dose related. However, there is scarcity of reports on symptomatic DILI occurring in patients on low dose statin and normal baseline liver function test. This case adds to the growing body of literature on the potential idiosyncratic, non-dose related adverse effects associated with atorvastatin therapy. Case report: A 69-year-old woman with history of Hypertension, Hyperlipidemia, Prediabetes, Non-Alcoholic Fatty Liver Disease (NAFLD) presented to her Primary care Physician (PCP) for regular follow up. Her Lipid panel in the last 1 year has been suboptimal with her Atherosclerotic Cardiovascular disease (ASCVD) risk score between 12.0-15.1% despite lifestyle modification. Patient was started on 10 mg of Atorvastatin daily after documenting normal baseline liver function test. Fifty-six days later, patient presented to the PCP’s office with symptoms of fatigue, nausea and, right upper abdominal pain for 3 days. She had right upper abdominal tenderness and was mildly icteric. Based on her PCPs suspicion for DILI, she was advised to discontinue atorvastatin and transferred to the emergency room for further evaluation. In the Emergency room her vitals remained stable. Liver Ultrasound showed normal sized liver with features of hepatic steatosis. Laboratory analysis showed elevated alanine aminotransferase (ALT) greater than 16 times Upper limit of normal (ULN), aspartate aminotransferase (AST) greater than 9 times ULN, while alkaline phosphatase (ALP) elevation was less than 2 times ULN suggesting hepatocellular pattern. She was seen by a hepatologist 1 week later and other etiologies of acute hepatitis were ruled out. Over the course of 4 weeks, her symptoms completely resolved and liver function tests continued to improve. Forty-six days after Atorvastatin was discontinued, her aminotransaminases returned to normal levels. Conclusion: Although DILI is usually dose dependent, this case emphasizes the need for constant monitoring of liver function test of patients on low dose statins including patients with normal baseline liver function test. Personalized medical approach involving validated predictive score for DILI may become increasingly important in tailoring statin therapy to minimize the risk of adverse effects.

Nationwide Big Data Analysis of Statin Use and Intracerebral Hemorrhage Risk in Acute Ischemic Stroke Patients in Taiwan.

Background and Objectives: Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used with an increased risk of intracranial hemorrhage. In this nested case-control study, we used Taiwan's nationwide universal health insurance database to investigate the possible association between statin therapy prescribed to acute ischemic stroke patients and their risk of subsequent intracerebral hemorrhage and all-cause mortality in Taiwan. Materials and Methods: All data were retrospectively obtained from Taiwan's National Health Insurance Research Database. Acute ischemic stroke patients were divided into a cohort receiving statin pharmacotherapy and a control cohort not receiving statin pharmacotherapy. A 1:1 matching for age, gender, and index day, and propensity score matching was conducted, producing 39,366 cases and 39,366 controls. The primary outcomes were long-term subsequent intracerebral hemorrhage and all-cause mortality. The competing risk between subsequent intracerebral hemorrhage and all-cause mortality was estimated using the Fine and Gray regression hazards model. Results: Patients receiving statin pharmacotherapy after an acute ischemic stroke had a significantly lower risk of subsequent intracerebral hemorrhage (p < 0.0001) and lower all-cause mortality rates (p < 0.0001). Low, moderate, and high dosages of statin were associated with significantly decreased risks for subsequent intracerebral hemorrhage (adjusted sHRs 0.82, 0.74, 0.53) and all-cause mortality (adjusted sHRs 0.75, 0.74, 0.74), respectively. Conclusions: Statin pharmacotherapy was found to safely and effectively reduce the risk of subsequent intracerebral hemorrhage and all-cause mortality in acute ischemic stroke patients in Taiwan.